Rates of mortality attributable to unintentional poisoning are rising rapidly as a consequence of both the medical and non-medical use of prescribed opioid analgesics. Project Lazarus, which was created to respond to North Carolina's epidemic of abuse of opioid analgesics, is a novel community-based drug overdose prevention program designed to reduce the supply of, demand for, diversion of and risks associated with opioid analgesics, while promoting the optimal treatment of chronic pain. A preliminary efficacy study has demonstrated dramatic effects on decreases in deaths attributable to opioid misuse and abuse without adversely affecting prescriptions for opioid analgesics. Now called the Project Lazarus/Chronic Pain Initiative (PL/CPI), Project Lazarus is collaborating with NC's Medicaid Authority to expand this initiative to all counties in the State. The goal of the intervention is to reduce the risks associated with opioid analgesics while maintaining appropriate access to these medications for control of chronic pain. We propose a two year effectiveness study to test whether this statewide community- based initiative: 1. increases providers' rates of registry and consultation with the State's prescription monitoring program, the Controlled Substances Reporting System (CSRS); 2. improves access to substance abuse treatment by increasing the number of individuals who receive medically-assisted treatment (MAT) for opioid dependence; 3. decreases monthly county-level drug-related emergency department (ED) visit rates attributable to opioid overdoses, using a unique statewide population-based ED surveillance system; and 4. is associated with a reduction in annual county-level age-adjusted opioid-related unintentional poisoning mortality rates. Substantial efficiencies in this natural quasi-experimental study will be achieved insofar as full support for the implementation of the PL/CPI is already available from NC's Medicaid Program and several foundations, thus limiting the resources we are requesting of the CDC to those that are required to conduct the evaluation itself. The highly innovative community-based opioid poisoning prevention strategies that constitute the PL/CPI are deserving of an evaluation and, if found to be effective, of replication across the country to respond to the nation' exploding epidemic of prescription drug overdose. PUBLIC HEALTH RELEVANCE: Deaths due to the abuse and misuse of opioid analgesics have nearly doubled in the U.S. in the last past 10 years, and the U.S. rates of ED visits related to narcotic analgesics rose by 155% between 2004 and 2009. There are now about 9000 daily cases of prescription opioid abuse, and their total costs to society as of 2009 were estimated at $56 billion, of which $25 billion were borne by the health care system. The proposed study would evaluate the first statewide implementation of a community and provider based opioid overdose prevention initiative in the nation.